RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of flavopiridol in treating patients who have previously untreated or relapsed mantle cell lymphoma.

Condition	Treatment or Intervention	Phase
stage I mantle cell lymphoma stage III mantle cell lymphoma stage IV mantle cell lymphoma recurrent mantle cell lymphoma stage II mantle cell lymphoma	Drug: flavopiridol  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Assess the efficacy of flavopiridol in terms of response rate in patients with previously untreated or relapsed mantle cell lymphoma.
• Assess the toxicity of this regimen in this patient population.
• Determine the time to progression and, if responses are observed, response duration in these patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive flavopiridol IV over 1 hour daily for 3 days. Treatment continues every 3 weeks in the absence of unacceptable toxicity or disease progression. Patients with a complete response (CR) receive 2 additional courses after documented CR. Patients with a partial response receive 2 additional courses after documented maximal tumor shrinkage. Patients with stable disease receive a maximum of 4 courses.

Patients are followed at 4 weeks and then every 3 months until relapse or death.

PROJECTED ACCRUAL: A total of 14-30 patients will be accrued for this study within 18-24 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed mantle cell lymphoma (at initial diagnosis) nonrefractory to prior therapy or with no prior therapy
• No documented disease progression while receiving prior chemotherapy
• CD20 and CD5 positive
• Presence of clinically and/or radiologically documented disease
• At least 1 site of disease must be bidimensionally measurable
• Bone lesions not considered bidimensionally measurable
• Minimum indicator lesions must be:
• Lymph nodes at least 1.5 cm x 1.5 cm by physical exam or spiral CT scan OR
• Other nonnodal lesions at least 1 cm x 1 cm by MRI, CT scan, or physical exam
• No known CNS involvement by lymphoma

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm3
• Platelet count at least 75,000/mm3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit or normal (ULN)
• AST no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No clinically significant cardiac symptomatology
• If history of cardiac disease, cardiac ejection fraction greater than 50%

Pulmonary:

• No clinically significant pulmonary symptomatology
• If history of symptomatic pulmonary disease:
• FEV1, FVC, and TLC greater than 60% predicted
• DLCO greater than 50% predicted

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Must be accessible for treatment and follow-up (i.e., no geographical limitations)
• No uncontrolled bacterial, fungal, or viral infection
• No other serious concurrent disease

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior radioactive monoclonal antibody therapy
• Prior rituximab allowed

Chemotherapy:

• See Disease Characteristics
• No more than 2 prior chemotherapy regimens allowed
• Same chemotherapy combination given for first line and second line therapy considered 2 regimens
• At least 6 weeks since prior chemotherapy
• No prior high-dose chemotherapy and stem cell transplantation
• No other concurrent cytotoxic chemotherapy

Endocrine therapy:

• No concurrent corticosteroids

Radiotherapy:

• No prior radiotherapy to greater than 25% of functioning bone marrow
• At least 4 weeks since prior radiotherapy (except low-dose, non-myelosuppressive radiotherapy) and recovered
• No concurrent radiotherapy to sole site of measurable disease

Surgery:

• At least 2 weeks since prior major surgery

Other:

• No other concurrent investigational anticancer agents

Canada, Nova Scotia
      Nova Scotia Cancer Centre, Halifax,  Nova Scotia,  B3H 1V7,  Canada
Canada, Ontario
      Cancer Care Ontario-Hamilton Regional Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
      Humber River Regional Hospital, Weston,  Ontario,  M9N 1N8,  Canada
      Toronto General Hospital, Toronto,  Ontario,  M5G 2C4,  Canada

Study chairs or principal investigators

Joseph Michael Connors, MD,  Study Chair,  British Columbia Cancer Agency   

Study ID Numbers:  CDR0000067679; CAN-NCIC-IND127; NCI-100
Record last reviewed:  May 2003
Last Updated:  October 13, 2004
Record first received:  April 6, 2000
ClinicalTrials.gov Identifier:  NCT00005074
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08